Pius’s pontificate, like his pre-papal career, was marked by great diplomatic activity, often aided by Eugenio Pacelli (later PopePius XII). He openly opposed the youth activities of Fascist governments, and he finally published the papal letter Non abbiamo bisogno in 1931; it showed one could not be both Fascist and Catholic. Relations between Mussolini and the Holy See deteriorated.

Hitler signed a concordat with the Church in 1933, but never paid it any attention after the ceremony. Nazis continually meddled with Church activities, persecuted clergy, and tried to convert GermanChristians to the new faith in Nazism. Pius denounced the government and Nazi theory in Mit brennender Sorge in 1937. Soon after, he issued the analysis On Atheistic Communism, denounced persecutions in Russia, Mexico, and Spain, and was on unusually good terms with England, Netherlands, and France.

Pius spoke out against nationalism, racism, anti-Semitism, and totalitarianism, and for human dignity. He established the new feast of Christ the King to recall the rights of religion in the state. He thought little of laissez-faire capitalism, and urged social reform in the 1931 encyclical Quadragesimo anno. He called for greater participation by the laity, a movement he called Catholic Action. He supported missionary work, but wanted to integrate Christianity with native cultures instead of making them European. To protect Eastern rite Catholics from Latin influence, he augmented their congregation, established a commission to study their canon law, and exhorted Western Catholics to embrace their brothers of the various Eastern rites. Pius loved technology, and sought ways for it to benefit the Church. He established Vatican radio, modernized the Vatican Library, and reconstituted the Pontifical Academy of the Sciences in 1936 with a large international membership.